14-59642862-A-G

Variant names:

• chr14-59642862-A-G
• rs12434215
• NM_021136.3:c.1766-35370T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021136.3(RTN1):​c.1766-35370T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,072 control chromosomes in the GnomAD database, including 10,558 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (10558 hom., cov: 32)
• Consequence: RTN1 NM_021136.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 8 publications found

Genes affected

RTN1 (HGNC:10467): (reticulon 1) This gene belongs to the family of reticulon encoding genes. Reticulons are associated with the endoplasmic reticulum, and are involved in neuroendocrine secretion or in membrane trafficking in neuroendocrine cells. This gene is considered to be a specific marker for neurological diseases and cancer, and is a potential molecular target for therapy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTN1	NM_021136.3	c.1766-35370T>C		intron_variant	Intron 3 of 8	ENST00000267484.10	NP_066959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTN1	ENST00000267484.10	c.1766-35370T>C		intron_variant	Intron 3 of 8	1	NM_021136.3	ENSP00000267484.5
RTN1	ENST00000432103.6	n.796-35370T>C		intron_variant	Intron 1 of 6	1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50868 AN: 151954 Hom.: 10556 Cov.: 32

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.314

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.335 AC: 50873 AN: 152072 Hom.: 10558 Cov.: 32 AF XY: 0.343 AC XY: 25484 AN XY: 74326

African (AFR) AF: 0.0806 AC: 3348 AN: 41538

American (AMR) AF: 0.357 AC: 5447 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1381 AN: 3472

East Asian (EAS) AF: 0.396 AC: 2047 AN: 5166

South Asian (SAS) AF: 0.309 AC: 1488 AN: 4820

European-Finnish (FIN) AF: 0.586 AC: 6174 AN: 10536

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29719 AN: 67962

Other (OTH) AF: 0.315 AC: 666 AN: 2112

Alfa AF: 0.402 Hom.: 6911

Bravo AF: 0.310

Asia WGS AF: 0.305 AC: 1067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.75
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12434215; hg19: chr14-60109580;